Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons

被引:55
作者
Drerup, Catherine M. [1 ,2 ]
Herbert, Amy L. [3 ]
Monk, Kelly R. [3 ]
Nechiporuk, Alex V. [1 ]
机构
[1] Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97201 USA
[2] NICHHD, NIH, Bethesda, MD 20892 USA
[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA
关键词
ACTIN-RELATED PROTEIN; POINTED-END COMPLEX; CYTOPLASMIC DYNEIN; ZEBRAFISH; DEGENERATION; REVEALS; KINESIN; RECRUITMENT; INITIATION; DYNAMICS;
D O I
10.7554/eLife.22234
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.
引用
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页数:25
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